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Interleukin 21 (IL-21) medicine for cancer therapy

An interleukin and tumor technology, applied in anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve problems such as unsatisfactory tumor treatment effects, and achieve the effects of preventing tumor recurrence, improving microenvironment, and enhancing curative effects.

Active Publication Date: 2012-11-14
乘典(苏州)生物医药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have found that systemic administration of IL-21 can enhance the response and effector function of CD8+ T cells and NK cells to exert anti-tumor effects [15, 16, 17], but the tumor treatment effect is not very satisfactory

Method used

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  • Interleukin 21 (IL-21) medicine for cancer therapy
  • Interleukin 21 (IL-21) medicine for cancer therapy
  • Interleukin 21 (IL-21) medicine for cancer therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Example 1. Intratumoral injection of IL-21 significantly enhanced the tumor therapeutic effect of anti-HER2 / neu antibody:

[0058] to normal wild-type Balb / c mice ( figure 1 A) or HER2 / neu antigen immunotolerant (HER2 / neu x Balb / c) F1 mice ( figure 1 B) Inoculate the tumor, and give anti-HER2 / neu antibody treatment when the tumor grows to a certain size, and at the same time inject recombinant IL-21 protein (Pepro Tech) into the tumor for combined treatment, which can significantly enhance the tumor therapeutic effect of anti-HER2 / neu antibody.

[0059] Specific experimental methods:

[0060] (1) Inoculate normal Balb / c mice subcutaneously with 8×10 5 Tubo tumor cells were divided into 4 groups, 5 mice in each group, anti-HER2 / neu antibody+IL-21 group: 100 μg anti-HER2 / neu antibody was intraperitoneally injected on day 16, and tumor cells were injected on day 16 and day 19. Intratumoral injection of 5 μg IL-21 protein (Pepro Tech); anti-HER2 / neu antibody group: intra...

Embodiment 2

[0062] Example 2. Intratumoral injection of IL-21 induces the polarization of tumor-associated macrophages to the M1 type, significantly improving the tumor immunosuppressive microenvironment:

[0063] Intratumoral injection of IL-21 into tumor-bearing mice significantly reduced the proportion of macrophages in tumor tissue ( figure 2 A), increasing anti-tumor effector cells (NK, CD8 + The proportion of T cells) ( figure 2 B) Induced tumor infiltrating macrophages with low expression of M2 macrophage factors CCL17, IL-10, TGF-β, VEGF, etc., and high expression of M1 type macrophage factors CXCL9, Nos2, etc. ( figure 2 C); Eliminate the inhibitory effect of TAM on T cell proliferation ( figure 2 D).

[0064] Specific experimental methods:

[0065] (1) Analysis of cell subsets in tumor tissue: Balb / c mice were subcutaneously inoculated with 8×10 5 Tubo tumor cells were injected with 10 μg of IL-21 protein (Pepro Tech) into the tumor on the 15th day after inoculation. Af...

Embodiment 3

[0074] Example 3. IL-21 directly induces macrophages to differentiate into M1 type:

[0075] In order to prove that the intratumoral injection of IL-21 induces the polarization of tumor-associated macrophages to the M1 type is the result of the direct effect of IL-21 on macrophages, we first demonstrated that intraperitoneal injection of IL-21 in mice can also significantly inhibit peritoneal macrophages. The cells expressed M2 macrophage factors CCL17, IL-10, TGF-β, Mrc-1 ( image 3 A); On this basis, I isolated mouse peritoneal macrophages and co-cultured with IL-21 in vitro, and cultured overnight can significantly inhibit the expression of peritoneal macrophages M2 macrophage factors VEGF and TGF-β ( image 3 B); In addition, IL-21 can also significantly increase the secretion of inflammatory cytokines TNF-β and IL-6 secreted by LPS-stimulated mouse peritoneal macrophages in vitro ( image 3 C); IL-21 directly acts on M2 tumor-infiltrating macrophages and can rapidly indu...

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Abstract

The invention relates to the field of cancer therapy and relates to fusion protein of interleukin 21 and an anti-Her2 / neu single-chain antibody, wherein the fusion protein is utilized to treat breast cancer.

Description

technical field [0001] The present invention relates to the field of tumor treatment. In particular, the invention relates to the use of interleukin-21 in the treatment of tumors. More specifically, the present invention relates to the treatment of breast cancer using a fusion protein of interleukin 21 and an anti-Her2 / neu single chain antibody. Background technique [0002] The body's immunity plays an important role in the occurrence and development of tumors. In recent years, studies have found that the body's anti-tumor immune response also plays an important role in the therapeutic effects of conventional tumor radiotherapy and chemotherapy. Tumor radiotherapy and chemotherapy lead to massive death of tumor cells, release tumor antigens and a series of "danger signals", activate the body's innate immune signaling pathway, promote the uptake, processing and presentation of antigens by antigen-presenting cells, and induce and enhance the body's anti-tumor immune response...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N15/62A61K39/395A61K47/48A61P35/00
Inventor 王盛典傅阳心徐萌
Owner 乘典(苏州)生物医药有限公司
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